tbuckley/cabot-search huggingface dataset:
Molecular targets, therapeutic agents and multitasking nanoparticles to deal with cancer stem cells: A narrative review
Authors: Abolfazl Doustmihan, Marziyeh Fathi, MirAhmad Mazloomi, Aysan Salemi, Michael R. Hamblin, Rana Jahanban-Esfahlan
Journal: Journal of Controlled Release (2023)

There is increasing evidence that malignant tumors are initiated and maintained by a sub-population of tumor cells that have similar biological properties to normal adult stem cells. This very small population of Cancer Stem Cells (CSC) comprises tumor initiating cells responsible for cancer recurrence, drug resistance and metastasis. Conventional treatments such as chemotherapy, radiotherapy and surgery, in addition to being potentially toxic and non-specific, may paradoxically increase the population, spread and survival of CSCs. Next-generation sequencing and omics technologies are increasing our understanding of the pathways and factors involved in the development of CSCs, and can help to discover new therapeutic targets against CSCs. In addition, recent advances in nanomedicine have provided hope for the development of optimal specific therapies to eradicate CSCs. Moreover, the use of artificial intelligence and nano-informatics can elucidate new drug targets, and help to design drugs and nanoparticles (NPs) to deal with CSCs. In this review, we first summarize the properties of CSCs and describe the signaling pathways and molecular characteristics responsible for the emergence and survival of CSCs. Also, the location of CSCs within the tumor and the effect of host factors on the creation and maintenance of CSCs are discussed. Newly discovered molecular targets involved in cancer stemness and some novel therapeutic compounds to combat CSCs are highlighted. The optimum properties of anti-CSC NPs, including blood circulation and stability, tumor accumulation and penetration, cellular internalization, drug release, endosomal escape, and aptamers designed for specific targeting of CSCs are covered. Finally, some recent smart NPs designed for therapeutic and theranostic purposes to overcome CSCs are discussed.
British Association of Dermatologists guidelines for biologic therapy for psoriasis 2023: a pragmatic update
Authors: Catherine H Smith, Zenas Z N Yiu, Tracy Bale, A David Burden, Laura C Coates, Elizabeth Eckert, Nicky Longley, Satveer K Mahil, Arlene McGuire, Ruth Murphy, Catherine Nelson-Piercy, Caroline M Owen, Richard Parslew, Richard T Woolf, Zahra Mansour Kiaee, Alina M Constantin, Martinsixtus C Ezejimofor, Lesley S Exton, M Firouz Mohd Mustapa
Journal: British Journal of Dermatology (2023)

The article provides a pragmatic update of the British Association of Dermatologists guidelines for biologic therapy for psoriasis.
Understanding exosomes: Part 1—Characterization, quantification and isolation techniques
Authors: Richard J. Miron, Yufeng Zhang
Journal: Periodontology 2000 (2023)

Abstract Exosomes are the smallest subset of extracellular signaling vesicles secreted by most cells with a diameter in the range of 30–150 nm. Their use has gained great momentum recently due to their ability to be utilized as diagnostic tools with a vast array of therapeutic applications. Over 5000 publications are currently being published yearly on this topic, and this number is only expected to dramatically increase as novel therapeutic strategies continue to be investigated. This review article first focuses on understanding exosomes, including their cellular origin, biogenesis, function, and characterization. Thereafter, overviews of the quantification methods and isolation techniques are given with discussion over their potential use as novel therapeutics in regenerative medicine.
<i>Shigella flexneri</i> utilizes intestinal signals to control its virulence
Authors: Rimi Chowdhury, Paulina D. Pavinski Bitar, Katherine E. Bell, Craig Altier
Journal: Gut Microbes (2023)

The enteric pathogens have evolved to utilize elements from their surroundings to optimize their infection strategies. A common mechanism to achieve this is to employ intestinal compounds as signals to control the activity of a master regulator of virulence. Shigella flexneri (S. flexneri) is a highly infectious entero-invasive pathogen which requires very few organisms to cause invasion of the colonic mucosa. The invasion program is controlled by the virulence master regulator VirF. Here, we show that the fatty acids commonly found in the colon can be exploited by S. flexneri to repress its virulence, allowing it to energetically finance its proliferation, thus increasing its pathogenicity. Colonic fatty acids such as oleic, palmitoleic and cis-2-hexadecenoic acid were shown to directly bind to VirF and mediate its prompt degradation. These fatty acids also disrupted the ability of VirF to bind to its target DNA, suppressing the transcription of the downstream virulence genes and significantly reducing the invasion of S. flexneri to colonic epithelial cells. Treatment with colonic fatty acids significantly increased the growth rate of the pathogen only under invasion-inducing conditions, showing that the reduction in the burden of virulence promotes a growth advantage. These results demonstrate the process by which S. flexneri can employ intestinal compounds as signals to increase its numbers at its preferred site of invasion, highlighting the mechanism by which the full spectrum of shigellosis is achieved despite a miniscule infectious dose. This highlights an elegant model of environmental adaption by S. flexneri to maximize the pathogenic benefit.
The edible plant microbiome: evidence for the occurrence of fruit and vegetable bacteria in the human gut
Authors: Wisnu Adi Wicaksono, Tomislav Cernava, Birgit Wassermann, Ahmed Abdelfattah, Maria J. Soto-Giron, Gerardo V. Toledo, Suvi M. Virtanen, Mikael Knip, Heikki Hyöty, Gabriele Berg
Journal: Gut Microbes (2023)

Diversity of the gut microbiota is crucial for human health. However, whether fruit and vegetable associated bacteria contribute to overall gut bacterial diversity is still unknown. We reconstructed metagenome-assembled genomes from 156 fruit and vegetable metagenomes to investigate the prevalence of associated bacteria in 2,426 publicly available gut metagenomes. The microbiomes of fresh fruits and vegetables and the human gut are represented by members in common such as Enterobacterales, Burkholderiales, and Lactobacillales. Exposure to bacteria via fruit and vegetable consumption potentially has a beneficial impact on the functional diversity of gut microbiota particularly due to the presence of putative health-promoting genes for the production of vitamin and short-chain fatty acids. In the human gut, they were consistently present, although at a low abundance, approx. 2.2%. Host age, vegetable consumption frequency, and the diversity of plants consumed were drivers favoring a higher proportion. Overall, these results provide one of the primary links between the human microbiome and the environmental microbiome. This study revealed evidence that fruit and vegetable-derived microbes could be found in the human gut and contribute to gut microbiome diversity.
The unique interplay of mitochondrial oxidative phosphorylation (OXPHOS) and immunity and its potential implication for the sex‐ and age‐related morbidity of severe COVID‐19 patients
Authors: Yinchuan Li, Lei Li, Guanghao Wu, Gangcai Xie, Lirong Yi, Jie Zhu, ShiYu Liang, Ya‐ru Huang, Juan Chen, Shaoyang Ji, Fei Sun, Rui‐tian Liu
Journal: MedComm (2023)

Abstract Aged male patients are more vulnerable to severe or critical symptoms of COVID‐19, but the underlying mechanism remains elusive. In this study, we analyzed previously published scRNA‐seq data from a large cohort of COVID‐19 patients, castrated and regenerated mice, and bulk RNA‐seq of a RNAi library of 400 genes, and revealed that both immunity and OXPHOS displayed cell‐type‐, sex‐, and age‐related variation in the severe or critical COVID‐19 patients during disease progression, with a more prominent increase in immunity and decrease in OXPHOS in myeloid cells in the males relative to the females (60–69 years old). Male severe or critical patients above 70 years old were an exception in that the compromised negative correlation between OXPHOS and immunity in these patients was associated with its disordered transcriptional regulation. Finally, the expression levels of OXPHOS and androgens were revealed to be positively correlated, and the responses of macrophages to android fluctuation were more striking than other types of detected immune cells in the castrated mice model. Therefore, the interplay of OXPHOS and immunity displayed a cell‐type‐specific, age‐related, and sex‐biased pattern, and the underlying potential regulatory role of the hormonal milieu should not be neglected.
Correction to: Targeted therapy for cisplatin‐resistant lung cancer via aptamer‐guided nano‐zinc carriers containing USP14 siRNA
Authors: Xinmin Zhao, Xianghua Wu, Huijie Wang, Songtao Lai, Jialei Wang
Journal: MedComm (2023)

[This corrects the article DOI: 10.1002/mco2.237.].
A mixed-methods review and meta-synthesis of fears of recurrence and progression in people with mental health conditions
Authors: Daelin Coutts-Bain, Louise Sharpe, Pirathat Techakesari, Madeline Anne Forrester, Caroline Hunt
Journal: Clinical Psychology Review (2023)

A fear that one's physical illness will recur or worsen has received substantial research attention over the past decade, most notably as fear of cancer recurrence. Indeed, such fear is known to be associated with poorer quality of life, adjustment, and psychopathology. However, fear of a recurrence or progression (FORP) of mental health conditions has received comparatively little study. The present review aimed to, 1) systematically review quantitative research on FORP in mental health regarding its association with age, gender, quality of life, mental health outcomes, and health behaviours, and 2) meta-synthesize qualitative research related to FORP to construct a transdiagnostic model. A qualitative meta-synthesis of 19 studies identified four subthemes underlying FORP (fear of symptoms, loss of progress, fear of death, and traumatic experiences). The three themes related to FORP were: inability to trust oneself, hypervigilance, and a low-risk low-reward lifestyle which was comprised of three subthemes (limiting relationships, limiting life goals, and fear of changing treatment). A quantitative systematic review of 15 studies found that FORP was strongly associated with worse quality of life, and greater depression, anxiety, psychotic symptoms, and medication adherence, but was not associated with age or gender. Hence, FORP can be understood transdiagnostically, and is generally associated with poorer mental health outcomes but may also predict adaptive health behaviours, such as appropriate medication adherence.
Erratum to “Tumor-associated Macrophage-derived Interleukin-23 Interlinks Kidney Cancer Glutamine Addiction with Immune Evasion” [Eur. Urol. 75(5) (2019) 752–763]
Authors: Qiang Fu, Le Xu, Yiwei Wang, Qi Jiang, Zheng Liu, Junyu Zhang, Quan Zhou, Han Zeng, Shanyou Tong, Tao Wang, Yangyang Qi, Baoying Hu, Hangcheng Fu, Huyang Xie, Lin Zhou, Yuan Chang, Yu Zhu, Bo Dai, Weijuan Zhang, Jiejie Xu
Journal: European Urology (2023)
Reply to Badar M. Mian. Prostate Biopsy: Hyperbole and Misrepresentation Versus Scientific Evidence and Equipoise. Eur Urol. 2024;85:99–100
Authors: Adrian Pilatz, Steven MacLennan, Roderick C.N. van den Bergh, Rajan Veeratterapillay, Muhammad Imran Omar, Yuhong Yuan, Phillip Cornford, Gernot Bonkat
Journal: European Urology (2023)
Corrigendum to “EASL-ILCA clinical practice guidelines on the management of intrahepatic cholangiocarcinoma” [J Hepatol (79) (2023) 181–208]
Authors: Domenico Alvaro, Gregory J. Gores, Joël Walicki, Cesare Hassan, Gonzalo Sapisochin, Mina Komuta, Alejandro Forner, Juan W. Valle, Andrea Laghi, Sumera I. Ilyas, Joong-Won Park, Robin K. Kelley, Maria Reig, Bruno Sangro
Journal: Journal of Hepatology (2023)
Analysis of 60 patients with relapsed or refractory T‐cell acute lymphoblastic leukemia and T‐cell lymphoblastic lymphoma treated with <scp>CD7</scp>‐targeted chimeric antigen receptor‐T cell therapy
Authors: Xian Zhang, Junfang Yang, Jingjing Li, Liyuan Qiu, Jianping Zhang, Yue Lu, Yan‐li Zhao, David Jin, Jianqiang Li, Peihua Lu
Journal: American Journal of Hematology (2023)

Abstract While the use of chimeric antigen receptor‐T (CAR‐T) therapy for T‐cell malignancies is in the early stage of clinical trials, it exhibits substantial potential to offer long‐term remission for patients with refractory/relapsed (R/R) T‐cell malignancies. In our phase I/II clinical trials, 65 pediatric and adult patients with R/R T‐cell acute lymphoblastic leukemia and lymphoblastic lymphoma (T‐ALL/LBL) were enrolled (NCT04572308 and NCT04916860). Of these, 60 participants (T‐ALL 35, T‐LBL 25) received a single dose of naturally selected anti‐CD7 CAR (NS7CAR) T cells at three levels: a low dose (5 × 10 5 /kg), a medium dose (1 to 1.5 × 10 6 /kg), and a high dose (2 × 10 6 /kg). On day 28, 94.4% of patients achieved deep complete remission (CR) in bone marrow. Among the 32 patients with extramedullary disease, 78.1% showed response, with 56.3% in CR and 21.9% in partial remission. The 2‐year overall survival and progression‐free survival (PFS) were 63.5% (95% CI 47.7–79.4) and 53.7% (95% CI, 38.9–68.6), with no difference between pediatric and adult patients. PFS was significantly higher among the 37 CR patients who proceeded with consolidation transplant than the 10 patients who did not with 1‐year PFS 67.2% (95% CI 51.9–82.4) versus 15.0% (95% CI 0–40.2), p &lt; .0001. Of the 10 CR patients without transplants, eight relapsed, while two sustained CR on day 128, and day 180, respectively. Cytokine release syndrome occurred in 91.7% of patients (grade 1/2 in 80.0%, grade 3/4 in 11.7%) and 5% of patients had neurotoxicity. NS7CAR‐T therapy is effective in treating R/R T‐ALL/LBL patients with promising PFS while maintaining a manageable safety profile.
Memory-based unsupervised video clinical quality assessment with multi-modality data in fetal ultrasound
Authors: He Zhao, Qingqing Zheng, Clare Teng, Robail Yasrab, Lior Drukker, Aris T. Papageorghiou, J. Alison Noble
Journal: Medical Image Analysis (2023)

In obstetric sonography, the quality of acquisition of ultrasound scan video is crucial for accurate (manual or automated) biometric measurement and fetal health assessment. However, the nature of fetal ultrasound involves free-hand probe manipulation and this can make it challenging to capture high-quality videos for fetal biometry, especially for the less-experienced sonographer. Manually checking the quality of acquired videos would be time-consuming, subjective and requires a comprehensive understanding of fetal anatomy. Thus, it would be advantageous to develop an automatic quality assessment method to support video standardisation and improve diagnostic accuracy of video-based analysis. In this paper, we propose a general and purely data-driven video-based quality assessment framework which directly learns a distinguishable feature representation from high-quality ultrasound videos alone, without anatomical annotations. Our solution effectively utilizes both spatial and temporal information of ultrasound videos. The spatio-temporal representation is learned by a bi-directional reconstruction between the video space and the feature space, enhanced by a key-query memory module proposed in the feature space. To further improve performance, two additional modalities are introduced in training which are the sonographer gaze and optical flow derived from the video. Two different clinical quality assessment tasks in fetal ultrasound are considered in our experiments, i.e., measurement of the fetal head circumference and cerebellar diameter; in both of these, low-quality videos are detected by the large reconstruction error in the feature space. Extensive experimental evaluation demonstrates the merits of our approach.
Multi-class point cloud completion networks for 3D cardiac anatomy reconstruction from cine magnetic resonance images
Authors: Marcel Beetz, Abhirup Banerjee, Julius Ossenberg-Engels, Vicente Grau
Journal: Medical Image Analysis (2023)

Cine magnetic resonance imaging (MRI) is the current gold standard for the assessment of cardiac anatomy and function. However, it typically only acquires a set of two-dimensional (2D) slices of the underlying three-dimensional (3D) anatomy of the heart, thus limiting the understanding and analysis of both healthy and pathological cardiac morphology and physiology. In this paper, we propose a novel fully automatic surface reconstruction pipeline capable of reconstructing multi-class 3D cardiac anatomy meshes from raw cine MRI acquisitions. Its key component is a multi-class point cloud completion network (PCCN) capable of correcting both the sparsity and misalignment issues of the 3D reconstruction task in a unified model. We first evaluate the PCCN on a large synthetic dataset of biventricular anatomies and observe Chamfer distances between reconstructed and gold standard anatomies below or similar to the underlying image resolution for multiple levels of slice misalignment. Furthermore, we find a reduction in reconstruction error compared to a benchmark 3D U-Net by 32% and 24% in terms of Hausdorff distance and mean surface distance, respectively. We then apply the PCCN as part of our automated reconstruction pipeline to 1000 subjects from the UK Biobank study in a cross-domain transfer setting and demonstrate its ability to reconstruct accurate and topologically plausible biventricular heart meshes with clinical metrics comparable to the previous literature. Finally, we investigate the robustness of our proposed approach and observe its capacity to successfully handle multiple common outlier conditions.
Current treatment strategies in managing side effects associated with domiciliary positive airway pressure (PAP) therapy for patients with sleep disordered breathing: A systematic review and meta-analysis
Authors: Stephanie K. Mansell, Nikesh Devani, Amar Shah, Silvia Schievano, Eleanor Main, Swapna Mandal
Journal: Sleep Medicine Reviews (2023)

Sleep disordered breathing is commonly treated with positive airway pressure therapy. Positive airway pressure therapy is delivered via a tight-fitting mask with common side effects including: leak, ineffective treatment, residual sleep disordered breathing, eye irritation, nasal congestion, pressure ulcers and poor concordance with therapy. This systematic review and meta-analysis aimed to identify the effectiveness of current treatment strategies for managing side effects associated with positive airway pressure therapy. Five databases were searched and 10,809 articles were screened, with 36 articles included in the review. Studies investigated: dressings, nasal spray/douche, chin straps, heated humidification and interfaces. No intervention either improved or detrimentally affected: positive airway pressure concordance, Epworth Sleepiness Score, residual apnoea hypopnea index or interface leak. The review was limited by study heterogeneity, particularly for outcome measures. Additionally, patient demographics were not reported, making it difficult to apply the findings to a broad clinical population. This review highlights the paucity of evidence supporting treatment strategies to manage side effects of positive airway pressure therapy.
Immune evasion on the nanoscale: Small extracellular vesicles in pancreatic ductal adenocarcinoma immunity
Authors: Jordan Fyfe, Danielle Dye, Norbaini Binti Abdol Razak, Pat Metharom, Marco Falasca
Journal: Seminars in Cancer Biology (2023)

Pancreatic ductal adenocarcinoma (PDAC) is a type of cancer alarmingly expanding in our modern societies that is still proving to be very challenging to counteract. This disease constitutes a quintessential example of the multiple interactions existing between the tumour and its surrounding microenvironment. In particular, PDAC is characterized by a very immunosuppressive environment that favours cancer growth and makes this cancer type very resistant to immunotherapy. The primary tumour releases many factors that influence both the microenvironment and the immune landscape. Extracellular vesicles (EVs), recently identified as indispensable entities ensuring cell-to-cell communication in both physiological and pathological processes, seem to play a pivotal function in ensuring the delivery of these factors to the tumour-surrounding tissues. In this review, we summarize the present understanding on the crosstalk among tumour cells and the cellular immune microenvironment emphasizing the pro-malignant role played by extracellular vesicles. We also discuss how a greater knowledge of the roles of EVs in tumour immune escape could be translated into clinical applications.
Brief Report: Tyrosine Kinase Inhibitors for Lung Cancers That Inhibit MATE-1 Can Lead to “False” Decreases in Renal Function
Authors: Monica F. Chen, Guilherme Harada, Dazhi Liu, Ray DeMatteo, Christina Falcon, Clare Wilhelm, Mark G. Kris, Alexander Drilon, Victoria Gutgarts
Journal: Journal of Thoracic Oncology (2023)
Reconsidering the Cutoff Value for Sensitive and Refractory Relapses in Extensive-Stage SCLC in the Era of Immunotherapy
Authors: Masahiro Torasawa, Hidehito Horinouchi, Shogo Nomura, Satoshi Igawa, Maiko Asai, Hidenobu Ishii, Hiroshi Wakui, Ryota Ushio, Tetsuhiko Asao, Yukiko Namba, Ryo Koyama, Daisuke Hayakawa, Isana Katayama, Hironari Matsuda, Shinichi Sasaki, Kazuhisa Takahashi, Yukio Hosomi, Katsuhiko Naoki, Yuichiro Ohe
Journal: Journal of Thoracic Oncology (2023)

Traditionally, relapsed SCLC has been classified as "sensitive" or "refractory" on the basis of cutoff values (60 or 90 d) for the duration between the last chemotherapy and disease progression. Nevertheless, these cutoff values are not derived from rigorous analytical methods, and their applicability to contemporary treatments remains uncertain.
Anti-atherosclerotic effects and molecular targets of ginkgolide B from Ginkgo biloba
Authors: Weile Ye, Jiaojiao Wang, Peter J. Little, Jiami Zou, Zhihua Zheng, Jing Lu, Yanjun Yin, Hao Liu, Dongmei Zhang, Peiqing Liu, Suowen Xu, Wencai Ye, Zhiping Liu
Journal: Acta Pharmaceutica Sinica B (2023)

Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases (CVDs), the world's primary cause of death. Ginkgo biloba, a well-known traditional Chinese medicine with notable cardiovascular actions, has been used as a cardio- and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries. Preclinical studies have shown that ginkgolide B, a bioactive component in Ginkgo biloba, can ameliorate atherosclerosis in cultured vascular cells and disease models. Of clinical relevance, several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases, such as ischemia stroke. Here, we present a comprehensive review of the pharmacological activities, pharmacokinetic characteristics, and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy. We highlight new molecular targets of ginkgolide B, including nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidase), lectin-like oxidized LDL receptor-1 (LOX-1), sirtuin 1 (SIRT1), platelet-activating factor (PAF), proprotein convertase subtilisin/kexin type 9 (PCSK9) and others. Finally, we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.